The long term objective of the work described in this proposal is to develop and apply new methods for the synthesis of complex natural products and related systems that have useful biological properties. The main focus of this work is the development and application of synthetic strategies for the preparation of naturally occurring compounds that contain the 1- oxadecalin subunit. The goals of the studies proposed are: 1) To demonstrate the utility of 1-oxadecalone derivatives as synthetic intermediates for the preparation of complex molecules. 2) To apply this strategy to the enantioselective synthesis of the PAF antagonist phomactin A 3) To apply this method to the enantioselective synthesis of the adenylyl cyclase activator forskolin. 4) To address issues of enantioselectivity in the dihydropyrone Diels-Alder reaction To realize these goals, the dihydropyrone Diels-Alder reaction will be used as a basis for 1-oxadecalone synthesis. The utility of this methodology for the synthesis of complex molecules will be demonstrated through enantioselective total syntheses of the natural products phomactin A and forskolin. Phomactin A is a specific platelet activating factor antagonist, and the preparation of this and related compounds for biological testing may have implications for the development of therapeutic agents for the treatment of inflammatory, respiratory, and cardiovascular diseases. Forskolin has been shown to activate a variety of membrane proteins, and displays a wide range of biological properties, including antihypertensive and bronchospasmolytic properties. Information gained from these studies will benefit health related fields in general by providing new strategies and technologies for the efficient, enantioselective preparation of biologically active compounds, and by providing materials for structure/activity determinations and biological testing. As such, these efforts may contribute to the development of new therapeutic agents. In addition, the strategies and methods developed over the course of this work are anticipated to be of general utility to the synthetic chemistry community for the preparation of complex molecules of biological interest.